Q1 2021 Exelixis Inc Earnings Call

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Operator: Good morning. Welcome to the X-Elexis first quarter 2020 financial results conference call. My name is Hall, and I'll be your operator for today. Hall is being recorded for. I'd now like to turn the call over to your host for today, Susan Hubbard, Executive Vice President of Public Affairs. That's the relation.

Susan T. Hubbard: Thank you, Daphne, and thank you all for joining us for the X-Alexis first quarter 2021 Financial Results Conference Call. Joining me on today's call are Mike Morrissey, our president and CEO, Chris Center, our chief financial officer, T.J. Haley, our executive vice president of commercial, and Gisa Schwab, our chief medical officer, who together will review our corporate financial, commercial, and development progress for the first Peter Lamb, our chief scientific officer, is also here and will join us for the question and answer session following our prepared remarks. During the call today, we will refer to financial measures not calculated according to generally accepted accounting principles.

Non-GAAP measures as well as tables deriving these measures from our GAAP results.

During the course of this presentation, we will be making forward looking statements regarding future events and the future performance of the company. This includes statements about possible developments regarding discovery product development regulatory commercial financial and strategic matters.

Actual events or results could of course differ materially we refer you to the documents we file from time to time with the SEC, which under the heading risk factors identify important factors that could cause actual results to differ materially from those expressed by the company verbally and in writing today, including without limitation risks and uncertainties related to.

Susan T. Hubbard: Please refer to today's press release, which is posted on our website, for an explanation of our reasons for using such non-gap measures, as well as tables deriving these measures from our gap results. During the course of this presentation, we will be making forward-looking statements regarding future events and the future performance of the company. This includes statements about possible developments regarding discovery, product development, regulatory, commercial, financial, and strategic matters. However, actual events or results could, of course, differ materially.

The product commercial success market competition regulatory review and approval processes.

The clinical trials compliance with applicable regulatory requirements, our dependence on collaboration partners and the level of costs associated with discovery product development business development and commercialization activities and with that I will turn the call over to Mike Alright. Thank you Susan and thanks to everyone for joining us on the call today.

Susan T. Hubbard: We refer you to the documents we file from time to time with the SEC, which, under the heading risk factors, identify important factors that could cause actual results to differ materially from those expressed by the company verbally and in writing today, including, without limitation, risk and uncertainties related to product commercial success, market competition, regulatory review, and approval processes, conducting clinical trials, compliance with applicable regulatory requirements, are dependent on collaboration partners and the level of cost associated with discovery, product development And with that, I will turn the call over to Mike.

Exports of started 2021 with the strong first quarter, where we saw significant revenue growth from the Cabo Nemo first line RCC launch and posted our highest quarterly net product revenue since the initial <unk> approval in 2016. Please.

Please see our press release that was issued an hour ago for our first quarter financial results and an extensive list of key corporate accomplishments.

We will keep today's prepared remarks short so we can get to your important questions. Obviously, we're thrilled with the early performance of the Cabo the <unk> launch in first line RCC, which we believe reflects the strength and breadth of the efficacy tolerability and quality of life data from the Checkmate <unk> trial.

Susan T. Hubbard: All right, thank you, Susan, and thanks to everyone for joining us on the call today. X-OXX started 2021 with a strong first quarter, where we saw significant revenue growth from the Cabo-Nevo first-line RCC launch and achieved their highest quarterly net product revenue since the initial Cabo Medics approval in 2016. Please see our press release that was issued an hour ago for our first quarter financial results and an extensive list of key corporate accomplishments. We'll keep today's prepared remarks short so we can get to your important questions.

We continue to build momentum with a combined 35% growth in revenue over the last two quarters and anticipate a near doubling of Cabo RCC revenues by the end of 2022, when we expect to exit with a $1 $5 billion annualized run rate in the U S. If our launch of assumptions and trajectory continue on its current.

Michael M. Morrissey: Obviously, we're thrilled with the early performance of the Cabo-Nevo launch in First Line RCC, which we believe reflects the strengths and breadth of the efficacy, tolerability, and quality of life data from the Checkmate 90-R trial. We continue to build momentum with a combined 35% growth in revenue over the last two quarters and anticipate a near doubling of Cabo RCC revenues by the end of 2022, when we expect to exit with a $1.5 billion annualized run rate in the U.S. If our launch assumptions and trajectory continue on their current course.

Of course.

Also in the first quarter, we advanced the key 2021 discovery development and regulatory activities. We remain on track to report top line results for the combo of Tesco doublet in first line HCC from Cosmic 312, and in metastatic CRP C from cosmic <unk> one cohort six.

And expect to file up to three new SMB is for Cabo across these indications pending positive results along with the filing for cosmic 311.

Michael M. Morrissey: Also, in the first quarter, we advanced key 2021 discovery, development, and regulatory activities. We remain on track to report top-line results for Cabo-Atezzo, double it in first-line HCC from Cosmic 312, and in metastatic CRPC from Cosmic-O-21 cohort 6, and expect to file up to three new SNDAs for Cabo across these indications, pending positive results, along with the filing for Co Our early clinical pipeline also advanced nicely in the quarter, with significant progress in the Xcel 092 program, the initiation of the phase one clinical trial of XL 102, our novel CDK7 inhibitor, and the IND filing for XBO2, which was accepted by the FTA in April.

Our early clinical pipeline also advanced nicely in the quarter with significant progress in the <unk> program. The initiation of the phase one clinical trial of <unk> hundred two our novel CDK <unk> inhibitor and the IND filing for <unk>, which was accepted by the FDA in April.

Our discovery and preclinical teams continue to make important progress towards the optimization and characterization of new development candidates for both small molecule and ADC programs, which we believe will provide the foundation for new clinical candidates in the near future.

I'll close here by saying that the ex what's his team has hit the ground running in 2021 and is building on the urgency and focus from our recent progress to maximize our chance for success across the range of milestones ahead of us.

I'm incredibly proud to say that we're coming out of COVID-19 stronger than ever as we drive our business forward to help cancer patients live longer and recover stronger so with that I'll turn the call over to Chris who will provide an update on our first quarter 2021 financial results Chris. Thanks, Mike for the first quarter of 2021. The company reported total revenues of 200 <unk>.

Michael M. Morrissey: Our discovery and preclinical teams continue to make important progress towards the optimization and characterization of new development candidates for both small molecule and EEC programs, which we believe will provide the foundation for new clinical candidates in the near future.

Michael M. Morrissey: I'll close here by saying that the Xlexis team is ready to hit the ground running in 2021 and is building on the urgency and focus from our recent progress to maximize our chance for success across the range of milestones ahead of us. I'm incredibly proud to say that we're coming out of COVID stronger than ever as we drive our business forward to help cancer patients live longer and recover stronger. So with that, I'll turn the call over to Chris, who will provide an update on our first quarter 2021 financial results. Chris?

$70 2 million total.

Total revenues for the quarter included Cabozantinib franchise net product revenues of $227 2 million.

Net product revenues in the first quarter of 2021 were impacted by higher demand for couple of medics and a decrease in wholesaler inventory.

<unk> ex wholesaler inventories decreased by approximately 300 units and when combined with the higher demand resulted in a decrease in our inventory weeks on hand from approximately $3. One weeks on hand in the fourth quarter of 2022, approximately $2 three weeks on hand in the first quarter of 2021.

Chris Shibutani: Thanks, Mike. For the first quarter of 2021, the company reported total revenues of $270.2 million. Total revenues for the quarter included Cabo Zanthe and franchise net product revenues of $227.2 million. Net product revenues in the first quarter were impacted by higher demand for Cabo Medics and a decrease in wholesaler and CaboMedics Hostel inventory decreased by approximately 300 units, and when combined with the higher demand, resulted in a decrease in our inventory weeks on hand for approximately 3.1 weeks on hand in the fourth quarter of 2020 to approximately 2.3 weeks on hand in the first quarter of 2013.

Chris Shibutani: Total revenues also included $43 million in collaboration revenues from Ipton, Decata, and Janetta. Our total operating expenses for the first quarter of 2021 were $274.8 million compared to $245.8 million in the fourth quarter 2020. SJ&A expense was the primary driver with an increase in total operating expenses, which was primarily employee-related expenses, including an increase in stock-based competition, also impacting our total operating expenses for the first quarter of 2021, was approximately $24 million in licensing up front and milestone fees, benefit from income taxes for the first quarter of 2021, with $3.6 million compared to a benefit of $300,000 in the fourth quarter of, The company reported gap net income of $1.6 million or zero cents per share on a fully diluted basis for the first quarter of 2021, company also reported non-gap net income of $28.5 million or nine cents per share on a fully diluted, Non-Gap net income excludes the impact of approximately $26.9 million of stock-based compensation expense net of the related income tax. Cash and Investments for the quarter ended March 31, 2021, was approximately $1.6 billion.

Total revenue is also included $43 million of collaboration revenues from Ipsen, Takeda and Genentech.

The total operating expenses for the first quarter of 2021 were $274 8 million compared to $245 8 million in the fourth quarter 2020.

SG&A expenses the primary driver of the increase in total operating expenses, which was primarily employee related expenses, including an increase of the stock based compensation expense also impacting our total operating expenses for the first quarter 2021.

Was approximately $24 million in licensing upfront and milestone fees.

<unk> from income taxes for the first quarter of 2021 was $3 6 million compared to the benefit of $300000 in the fourth quarter of 2020.

The company reported GAAP net income of $1 6 million or zero cents per share on a fully diluted basis for the first quarter of 2021. The company also reported non-GAAP net income of $28 5 million or <unk> <unk> per share on a fully diluted basis.

Non-GAAP net income excludes the impact of approximately $26 9 million of stock based compensation expense net of the related income tax effect.

Cash and investments for the quarter ended March 31, 2021 was approximately $1 6 billion.

Finally, turning to our financial guidance for the full year of 2021, we're maintaining the financial guidance that we provided earlier this year and with that I'll turn the call over to P. J.

Thank you Chris today, I will discuss the <unk> business with regards to Q1 2021, particularly in the context of the first approval for <unk> in combination with an immune checkpoint inhibitor.

As you know on January 20 <unk>.

<unk> received FDA approval for use in first line RCC in combination with Nova overlap.

Chris Shibutani: And finally, turning to our financial guidance for the full year of 2021, we are maintaining the financial guidance that we provided earlier this year. And with that, I'll turn the call over to PJ. Thank you, Chris.

The team was fully prepared to hit the ground sprinting and we're pleased with the execution of the launch which is resulting in rapid and importantly broad uptake of <unk>.

Patrick J. Haley: Today I will discuss the Cabometics business with regard to Q1 2021, particularly in the context of the first approval for CaboMedics in combination with an immune checkpoint inhibitor. As you know, on January 22nd, Cabometics received FDA approval for use in first-line RCC in combination with Navolam. The team was fully prepared to hit the ground sprinting, and we were pleased with the execution of the launch, which is resulting in rapid and importantly broad uptake of CaboMedica. Cabometics was the only TKI in Q1 among the TKIs in Leida, Sutton, and Votriant, or the CISV market basket to grow NRX market share, increasing from 32% in Q4 to 36%, according to Acu

<unk> was the only <unk> in Q1, among the Cabo medics, and lighter sutent and <unk> or <unk> market basket to grow in Rx market share increasing from 32% in Q4 to 36% According to <unk> data.

Importantly, <unk> and Rx volume grew 31% Q1, 2021 over Q4, 2020, driven primarily by uptake of the combination of Cabo in the euro in the first line setting.

Additionally, <unk> Rx volume increased by 21% in Q1 relative to Q4 of 2020.

We are also pleased adoption was broad across a number of key segments with strong uptake in favorable intermediate and poor clinical risk groups as the 90 of our data is resonating with physicians broadly as they think about patients who are appropriate for the regimen.

Patrick J. Haley: Importantly, CaboMedics' NRX volume grew 31% in Q1, 2021 over Q4 2020, driven primarily by uptake of the combination of Cabo and Neo in the first line setting. Additionally, Cabomedx volume increased by 21% in Q1 relative to Q4 of 2020. We are also pleased adoption was broad across a number of key segments with strong uptake in favorable, intermediate, and poor clinical risk groups as the 90R data is resonating with physicians broadly as they think about patients who are appropriate for the regimen.

Our market research shows the Cabo <unk> combination with Evo is taking share from all first line competitors already at this early stage of the launch.

Beyond these initial metrics, we won't be providing other details for competitive reasons, specifically market share by line of therapy, which I am sure you can appreciate it.

Uptake in the academic segment has been rapid and we're seeing strong adoption in the community setting as well.

We believe there is significant opportunity for continued growth in new patient market share, particularly in the community setting.

Patrick J. Haley: Our market research shows that Cabo Medicine, in combination with Nivo, is taking share from all first-line competitors already at this early stage of the line. Beyond these initial metrics, we won't be providing other details for competitive reasons, specifically market share by line of therapy, which I am sure you can appreciate. Uptake in the academic segment has been rapid, and we are seeing strong adoption in the community setting as well. We believe there is significant opportunity for continued growth in new patient market share, particularly in the community setting. Recently, we have begun to see many community accounts begin to reopen access to industry representatives given the improving trends in the pandemic.

Recently, we have begun to see many community accounts begin to reopen access to industry representatives, given improving trends in the pandemic.

While this is variable depending on the account and geography. Our belief is that this will continue to improve facilitation of education and discussions of the 90 of our data, which prescribers find compelling and important for their patients with RCC, who have yet to receive the therapy.

This trend coupled with our comprehensive launch plan for execution of both virtual and in person tactics should.

Should continue to drive new patient market share in the community setting.

Patrick J. Haley: While this is variable depending on the account and geography, our belief is that this will continue to improve facilitation of education and discussions of the 90R data, which prescribers find compelling and important for their patients with RCC who have yet to receive therapy. This trend, coupled with our comprehensive launch plan for execution of both virtual and in-person tactics, should continue to drive new patient market share in the community setting. In addition to the broad uptake of Kabometix plus Nivo in the marketplace, perceptions of the 90-yard data have been very positive.

In addition to the broad uptake of <unk> plus <unk> in the marketplace perceptions of the 90 of our data have been very positive.

There has been a rapid increase in unaided awareness of the approval of this combination as well as favorable impressions of the efficacy of the combination.

Based on the endpoint of OS PFS and <unk> across the key subgroups, including MDC risk categories.

Importantly, the safety profile of the combination driven by the optimized Cabo combination starting dose of 40 milligrams daily is viewed favorably by prescribers. It is improving the overall perceptions of safety and Tolerability of Cabo mix.

Patrick J. Haley: There has been a rapid increase in unaided awareness of the approval of this combination, as well as favorable impressions of the efficacy of the combination based on the endpoints of OS, PFS, and ORR across key subgroups, including IMDC risk categories. Importantly, the safety profile of the combination driven by the optimized Cabo combination starting dose of 40 milligrams daily is viewed favorably by prescribers and is improving the overall perceptions of safety and tolerability of Cabo. Physicians also view the quality of life benefit demonstrated in 9ER as differentiating and important for their patients who may be on first-line therapy for extended lengths of time. The Exilix of teams continuing strong and focused execution on the line.

Physicians also view of the quality of life benefit demonstrated 90 or is differentiating and important for their patients who may be on first line therapy for extended length of time.

The <unk> team is continuing strong and focused execution on the launch the.

These efforts are aided by the recently published Cabozantinib data at <unk>, including the presentation focused on quality of life.

Furthermore, the publication of 90 or in the New England Journal of Medicine on March 3rd.

And the recent update of the NCC and guidelines on April 21.

Gisa Schwab: These efforts are aided by the recently published Cabosanin date at ASCOGU, including a presentation focused on quality of life. Furthermore, the publication of 9ER in the New England Journal of Medicine on March 3rd, and the recent update of the NCCN guidelines on April 21st, which positioned Khabazantin and Plus Novolamath is the only FDA-approved, preferred, category one regimen across all clinical risk groups should continue to support the broad uptake of the combination, strong Q1 performance in Cabo Medics launch trajectory positioned the Cabo's Antitin franchise to continue significant revenue growth in 2021 and beyond.

Gisa Schwab: We're thrilled with the opportunity that 9E provides Exilixus looking forward as we continue to build upon the foundation in RCC where Cabometics is the number one prescribed TKI. Beyond 9ER, we're already working on plans to optimize potential future access to Khabo's Antinib Development Program as it moves forward broadly across multiple indications and with different combination partners. We look forward to building on this momentum in RCC, HCC, DTC and other potential future indications, such as prostate and lung, as our development program evaluating Kaba in combination with immune checkpoint inhibitors advances.

Cool.

Thank you P. J I'm pleased to provide an update on the development programs.

'twenty one is certainly off to a great start for our Cabozantinib regulatory and development program as.

Well as of two of our growing clinical pipeline programs, including excel on the IDE true ex.

Gisa Schwab: Our team remains highly focused and motivated to compete every day to bring the benefit of Kaumetics to all eligible patients as we continue to build the franchise and maximize its clinical and commercial potential.

For the two and ex speak or true.

Starting with the Cabozantinib the regulatory progress.

Oh of January 'twenty, 'twenty, one approval by FDA for the Cabozantinib and the volume of combination for the first line treatment of.

Gisa Schwab: Thank you, PJ. I'm pleased to provide an update on the development program. 2021 is certainly off to a great start for our Khabizankanib Regulatory and Development Program, as well as for our growing clinical pipeline programs, including X-O-92, XL102, and XB-O-O-O-2. Starting with the Kabazantan of regulatory progress.

Patients with advanced RCC.

The combination of achieved a positive <unk> opinion in the EU in February.

And quickly thereafter in late March the European Commission approved the combination of where the first VAG treatment of RCC patients in the EU.

Yeah.

After having reported exciting presentations and advanced RCC at ask Oh, Gee, you hook up the downturn at the in combination with new volume up from.

Gisa Schwab: After our January 2021 approval by FDA for the Khabizantinip and the Volumup combination for the first-line treatment of patients with advanced RCC, the combination achieved a positive CHMP opinion in the EU in February, and quickly thereafter in late March, the European Commission approved the combination for the first-line treatment of RCC patients in the EU. After having reported exciting presentations in Advanced RCC at ASCOGU for Kabazantinip in combination with New Volume Up from Checkmate 9ER, as well as single agent Kabazantinip results, including from the PEP study.

Checkmate nine New York as well as a single agent Cabozantinib results, including from the published study.

Now looking forward to the upcoming ethical conference with further data presentations and based on the Checkmate <unk> study and also single agent results from Cosmic 311 of phase three trial in differentiated thyroid cancer.

Turning to an update on our ongoing program for Cabozantinib.

We have continued execution of the cosmic <unk> one of 311 of 312 and $3 15 studies and are on track for milestones on these trials as previously shared including the three potential new cabozantinib as the NDA filings.

Gisa Schwab: We are now looking forward to the upcoming ASCO conference with further data presentations based on the Technic 90R study and also single agent results from Krasnix 3-11, our phase 3 trial in differentiated thyroid tests. Turning to an update on our ongoing program for Kabazan, we have continued our execution of the Cosmic 021, 311, 312, and 313 studies and are on track for milestones on these trials, as previously shared, including three potential new Kabazan-SNP S&A filings. I'll provide a brief summary of the key highlights of the program.

I'll provide a brief summary on key highlights for the program.

So of cosmic 311 in radioiodine refractory DTC patients who have received prior of the GFR targeted therapy. We are working towards an NDA submission based on the strong results in a patient population with unmet medical needs.

As announced previously the trial met its primary endpoint of progression free survival with Cabozantinib, the highly significantly improving the progression free survival versus placebo and FDA granted breakthrough therapy designation for the indication of during the quarter.

Gisa Schwab: For Cosmic 311 in radioiodon refractory DTC patients who have received priorvegar targeted therapy, we are working towards an SNDA submission based on the strong results in a patient population with unmit medical condition. As announced previously, the trial met its primary endpoint of progression-free survival, with Kabazantinib highly significantly improving progression-free survival versus placebo, and FDA granted a breakthrough therapy designation for the indication Based on these results, we are focused on an SMDA filing that we expect to complete in the second quarter. Cosmic 312, our phase 3 trial of Kabazaninep plus Atesolidimup versus seraphidip for the first-line treatment of advanced HCC, completed a cruel in the global study in mid-2020.

Based on these results we are focused on an NDA filing that we expect to complete in the second quarter.

Cosmic 312, all of phase III trial of Cabozantinib, plus the two the lease them up versus Sorafenib for the first line treatment of advanced H D. T completed it cool and the global study in mid 2020.

And we anticipate top line results of the event driven fee if that's the analysis.

And the concurrent interim analysis for overall survival in the second quarter of 2021 and.

And if warranted by the data.

And the result, we are expecting to file an NDA in the fourth quarter of 2021.

Yeah.

For cosmic Ultra one we look forward to the final analysis of score of objective response rate, but the independent Radiology Committee.

Gisa Schwab: And we anticipate top-line results of the event-driven PFS analysis and the concurrent interim analysis for overall survival in the second quarter of 2021; and, if warranted by the data and results, we are expecting to file an SNDA in the fourth quarter of 2021. For Cosmic 021, we look forward to the final analysis for objective response rate by the Independent Radiology Committee of cohort 6 in metastatic CRPC in mid-2020 and plan for regulatory submission of the results data.

Of cohort six and then aesthetic CRP C and made the 2021.

And the plan for regulatory submission of <unk>.

The results of data providing.

And that slipped from cosmic 313, comparing the triplet of Cabozantinib and the volume of and if you look them up versus new volume up and pull them up and first line RCC patients with intermediate or poor risk of per I M. D. C. We completed patient enrollment in late March and we are.

Now looking forward to top line results of the event driven analyses for the study in 'twenty or 'twenty two.

For the ongoing contact of phase III programs under our collaboration with Roche we are at.

Gisa Schwab: Lastly, for Cosmic 313, comparing the triplet of Krabazaninep, Nevolumab, and Epilumumab versus Nevolumub and Epilumumab in first-line RCC patients with intermediate or poor risk per IMDC, we completed patient enrollment in late March, and we are now looking forward to top-line results of the event-driven analyses for the study in 22.

The flea enrolling patients globally across all three phase III trials and checkpoint inhibitor pretreated, non small cell lung cancer and RCC patients.

And in novel Hormonal therapy, Pretreated CRP C patients.

So in summary, the Cabozantinib program continues to make significant progress and we remain on track for data Readouts in the next couple of months as well as of day to providing potential supplemental NDA findings.

Gisa Schwab: For the ongoing contact phase three program, under our collaboration with Roche, we are actively recruiting patients globally across all three phase three trials in Checkpoint Inhibitive, Pre-Treated Non-Smouse, Lung Cancer, and RCC patients, and in novel hormonal therapy, pre-treated CRPC patients. So, in summary, the Kabazanin program continues to make significant progress, and we remain on track for data redos in the next couple of months, as well as data providing potential supplemental NDA findings. I'll now turn to the progress on our XL-O-92 program and our new I-ND of Phase 1 programs for Excel 102 and XOOO2 and XB-O-O-2. First, Excel 09.

I'll now turn to the progress on our excellent on line two program and our new R&D of phase one programs for ex the one or two and XP or true.

First excel on line two.

Our next generation matched actual merger and much of our charging kinase inhibitor with a short of pharmacokinetic half life is advancing in phase one and we are in the midst of evaluating the combination with the kids of lease them up in a parallel phase one be part of the study.

Importantly, we have recently entered into a clinical collaboration agreement with Merck of K G. A a under which we will evaluate except when I joined combination with volume up and various your appeal you'll cancer cohorts.

Gisa Schwab: Our next generation, Metaxyl, Mur, and Medchifar Characin Kinase inhibitors with a shorter pharmacokinetic half-life, is advancing in phase one, and we are in the midst of evaluating the combination with tizolidemab in a parallel phase 1 B part of the study. Importantly, we have recently entered into a clinical collaboration agreement with Merck KGAA, under which we will evaluate XL092 in combination with Avalumub in various urophelial cancer cohorts, including in the maintenance setting of the prior first light platinum-containing chemotherapy, as well as in the second light setting in patients who have failed prior checkpoint inhibitor therapy.

Including in the maintenance setting after prior of first line platinum containing chemotherapy as well as in the second line setting and patients who have failed prior checkpoint inhibitor containing therapy.

And further we are actively discussing additional combination approaches with various checkpoint inhibitors and agents targeting novel mechanisms pre clinically and clinically to continue to define the opportunity for this important development program.

We have a deep and solid foundation, and a tyrosine kinase inhibitors and extensive experience with cabozantinib.

And see many opportunities to build on and expand on the therapeutic settings as we plan for potential tumor indications and lines of therapy, but excel or nine two combinations.

Gisa Schwab: Furthermore, we are actively discussing additional combination approaches with various checkpoint inhibitors and agents targeting novel mechanisms, preclinically and clinically, and in clinics, to continue to define opportunities for this important development program. We have a deep and solid foundation in tyrosine kinase inhibitors and extensive experience with Kobazantanin and see many opportunities to build on and expand on the therapeutic settings as we plan for potential tumor indications and lines of therapy for our Xcel092 combinations.

Given this extensive experience review of the XL on a true development risk profile, it's potentially being greatly improved versus more typical early stage programs.

So with that we are driving all of it so on a true development plan forward.

That includes a broad and comprehensive program across various tumor indications line.

The lines of therapy, and setting of broad therapeutic interest.

We intend to pursue the comprehensive evaluation of ex one I true in combination with various established checkpoint inhibitors and potential new combinations, including promising new checkpoint inhibitor of tablets as well most of the combination partners.

Gisa Schwab: Given this extensive experience, we view the XL092 development risk profile as potentially being greatly improved versus more typical early stage programs. So with that, we are driving our Xcel O92 development plan forward. That includes a broad and comprehensive program across various tumor indications, lines of therapy, and settings of broad therapeutic interest. For example, we intend to pursue the comprehensive evaluation of Xcelonite 2 in combination with various established checkpoint inhibitors and potential new combinations, including promising new checkpoint inhibitors, as well as other combination partners.

With the go to potentially start late stage because of the trials as soon as 2021, we are focusing on advancing our phase <unk> dose ranging in combination with checkpoint inhibitors rapidly to move into expansion cohorts that may support data driven of late stage development options across.

The variety of tumor types.

And secondly, we are excited to report progress with our latest the R&D candidates in 2021.

Gisa Schwab: With the goal to potentially start late-stage pivotal trials as soon as 2021, we are focusing on advancing our phase 1 B dose range in combination with checkpoint inhibitors rapidly to move into expansion cohorts that may support data-driven late-stage development options across a variety of tumor types. And secondly, we are excited to report progress with our latest I&D candidates in 2021. For F-SL- or two oral CDK-7 inhibitors, we have already started the phase one trial, and the cohort dose escalation phase is ongoing.

So one or two O R O C. The case seven inhibitor.

They have already started the phase one trial and the cohort dose escalation phase is ongoing.

And also we have recently announced the Fda's acceptance of the XP Oh, two I N D plus.

The first biologic product candidate.

Ex B O two an antibody drug conjugate or ADC targeting tissue factor that's been rationally designed such that the binding site of the antibody does not interfere with the coagulation cascade.

Based on this design and the available preclinical profile, we believe that ex the O O. Two may have the potential sort of best in class ADC targeting tissue factor.

Gisa Schwab: And also, we recently announced FDA's acceptance of the XPO2 I&D for our first biologic product candidate, XPOO2, an antibody drug conjugate or ADC targeting tissue factor. XPOO2 has been rationally designed such that the binding site of the antibody does not interfere with the coagulation cascade. Based on this design and the available preclinical profile, we believe that XPO2 may have the potential to be a best in class ADC targeting tissue. They're looking forward to progress on the phase one studies for both. The trials have been designed as efficient dose escalation trials with disease-specific expansion courts to allow for early assessment of initial antitumor activity, and I look forward to updating you on progress in our clinical pipeline in the future. And with that, I'll hand the call back to Mike.

We're looking forward to progress on the phase one studies for both compounds.

The trials have been designed as efficient dose escalation trials with disease specific expansion cohorts to allow for early assessment of the initial antitumor activity.

And I look forward to updating you on progress in our clinical pipeline in the future.

And with that I'll hand, the call back to Mike.

Alright. Thanks, Good luck as you heard on the call today, we're off to a great start in 2021.

Just last week, we marked the fifth anniversary of the first regulatory approval and launch of <unk> from the U S debt.

Also based on best in class data for Cabo in the Phase III Meteor trial in second line RCC some excellent for us on the path to the company the company. It is today.

Over the last five years, we have expanded the opportunity for cabozantinib to treat patients with thyroid renal and liver cancer and of helped tens of thousands of patients from the U S and a similar number of globally with our partners Ipsen and Takeda.

Michael M. Morrissey: All right, thanks, Gisla. As you heard on the call today, we're off to a great start in 2021. Just last week, we marked the fifth anniversary of the first regulatory approval and launch of ComboMedics in the U. That milestone, based on best in class data for Cabo in the phase three meteor trial in second line RCC, set Exilex on the path to becoming the company it is today. Over the last five years, we've expanded the opportunity for Capposanin to treat patients with thyroid, renal, and liver cancer and have helped tens of thousands of patients in the U.S. and a similar number globally with our partners, Ipsen and Cicada.

We're so excited about the potential of our work, including the ongoing cabozantinib pivotal trials the growing clinical development program for <unk>, two and our diverse and rapidly maturing early stage pipeline as we advance in our mission to help cancer patients live longer and recover stronger.

Of course today by thanking everyone of extra lessons for the Emerson in the first quarter and their individual and collective commitment dedication and resilience under what we're obviously extremely challenging conditions during the COVID-19 as.

Michael M. Morrissey: We're so excited about the potential of our work, including the ongoing Cabo Xanthenet Ptifital Trials, the growing clinical development program for XL092, and our diverse and rapidly maturing early-stage pipeline as we advance in our mission to help cancer patients live longer and recover stronger. I'll close today by thanking everyone at Exilexas for their efforts in the first quarter and their individual and collective commitment, dedication, and resilience under what were obviously extremely challenging conditions during COVID.

As I mentioned in my intro, we're exiting of global pandemic stronger than when it started for two months ago, and that's a true Testament to the quality of the people we have working day in and day out as we discover develop and commercialize the next generation of our medicines for cancer patients in need of better and more effective therapies.

We look forward to updating you on our progress in the future and thank you for your continued support and interest in ex the Lexus perhaps.

I'll now open the call for questions and definitely please proceed.

Michael M. Morrissey: As I mentioned in my intro, we're exiting a global pandemic stronger than when it started 14 months ago, and that's a true testament to the quality of the people we have working day in and day out as we discover, develop, and commercialize the next generation of our medicines for cancer patients in need of better and more effective therapy. We look forward to updating you on our progress in the future, and thank you for your continued support and interest in Exilex.

Thank you at the.

Time, if he would like to ask a question press star followed by the number one on your telephone keypad.

If you would like to withdraw your question press the pound key.

Please stand by while we compile the Q&A roster.

Your first question comes from the line of.

Michael M. Morrissey: We're happy to not open the call for questions, and Daphne, please proceed. Thank you. Would you like to ask a star, Balabae bat, or would you like to withdraw your question? Standby while we compiled the Q&A roster. Your first, Astika, warning with truest security. Hi, and Daphne, thanks for getting my name almost right there.

As the Guy.

Ooh warranty with true of Securities.

Please proceed.

Hi, guys and definitely that's the getting my name of almost right there.

[laughter].

Guys didn't fit together and got some of the quarter and in the <unk>.

Drunk cargo a rebound of yourself.

P. J I was wondering I know you don't want to give too much detail, but I was born free it's a good maybe a share with us which of the first line competitors. If you recall the knievel, maybe getting more share than some of the others.

And then I got a couple of questions for Q4.

Yeah. Thanks for the question asked the cut in.

Patrick J. Haley: I guys could speak together and congratulate each other on the quarter and the strong Cabo rebound that we saw. T.J., I was wondering, I know you don't want to give too much detail, but could maybe share with us which of the first-line competitors you feel like Cabo Nevo might gain more share than some of the others? And then I got a couple of, Yeah, thanks for the question, Ashtika. And, yeah, we're extremely pleased with the beginnings of the launch.

Really pleased with the beginnings of the launch.

What I guess I will say is as I mentioned in my prepared remarks extremely pleased with the.

The rapid broad uptake across not only competitive segment the segments, but clinical risk categories favorable intermediate poor.

Academic and community so I won't go into lot more detail.

With respect to that in the numbers, but what I will say is as we.

As we look at the quarter, we're approved as I mentioned you in late January so it basically of two full months of on the market.

Patrick J. Haley: You know, what I guess I'll say is, as I mentioned in my prepared remarks, I'm extremely pleased with the rapid, broad uptake across not only competitive segments but clinical risk categories, favorable, intermediate, poor, academic, and community. So I won't go into a lot more detail with respect to that and the numbers, but what I will say is as we look at the quarter, we were approved, as I mentioned in late January, so we've basically had two full months on the market.

February and March and if we look at our new patient market share in those two months.

We're very pleased that we see.

Our market share in the mid teens at that point the victory in a good direction exiting the quarter. So so we're very pleased with the.

Right Desma I was thinking about the so to sort of them of the Dow team is already in the clinic the sum of the tumor types.

You have outlined in your plant the XP or true, but not all of them could you tell us based on the tissue factor expression and the higher dosing that you can push with XP or two where do you think you might have an edge over to sort of mob.

Patrick J. Haley: February and March, and if we look at our new patient market share in those two months, we're very pleased that we see a market share in the mid-teens at that point, and, you know, vectoring in a good direction exiting the quarter, so we're very pleased with that. Right, Disa, I was thinking about this, so Tidotum is already in the clinic for some of the tumor types that you have outlined in your plan for XPO2, but not all of them, tell us, based on tissue factor expression and the higher doses that you can push with XPO2, where do you think you might have an edge over Sotomab?

Thanks.

Yeah.

Sure. Thank you for the question and I.

Think of them as I mentioned, we see opportunities for ex the old true and.

Its rationale of design in that.

The antibody does not bind and the way that it would interfere with the coagulation cascade, which should hopefully and Ah trends refer into a favorable safety profile and number one number two tissue factor, it's pretty broadly expressed.

Patrick J. Haley: Sure, thank you for the question. I think, as I mentioned, we see opportunity for XTO2, because of its rational design and that the antibody does not bind in a way that it would interfere with the coagulation cascade, which should hopefully translate into a favorable safety profile.

And we intend to evaluate the compound.

Lots of variety of tumor types and are assessing of course the expression profiles in.

In the patient population and attract the program forward Accordingly, as we are collecting clinical data.

Think of we have of broad opportunity and intend to pursue it aggressively.

He asked the comp.

Gisa Schwab: Number one, number two, tissue factor is pretty broadly expressed, and we intend to evaluate the compound across a variety of tumor types, assessing, of course, expression profiles in the patient populations and driving the program forward accordingly as we collect clinical data. So I think we have a broad opportunity and intend to pursue it aggressively. Hey, Astica, maybe Peter could provide some color commentary here too.

Maybe maybe maybe Peter could.

Some color commentary here too.

Yes.

To add onto it towards the flow.

The difference in addition to the normal episodes of the antibody, which has the advantages you outlined.

It does contain a kind of next generation will hit the linker construct which we believe has some advantages over the <unk>.

First generation construct this is one of the work has been.

Advanced and developed.

And then from the.

The expression point of view of piece of let's say of tissue factor is fairly broadly expressed obviously we of clinical proof of concept. There is clinical proof of concept of cervical cancer.

Peter Lawson: Yeah, just to add to what Giesler said, in addition to the novel epitope for the antibody, which has the advantages she outlined, it does contain a next-generation warhead linker construct, which we believe has some advantages over the first-generation constructs. This is one that Zymeworks has advanced and developed. And then from an expression point of view, as Giesler said, tissue factors are fairly broadly expressed.

Beyond that we actually presented prequel iconic presented preclinical data late last year in pancreatic I think head and neck gastric cancer and there were several of the only two months that we haven't explored preclinical yet so the opportunities growth.

Great Thanks for that guidance.

Your next question comes from the line of Jason Gursky.

Peter Lawson: Obviously, we have clinical proof of concept, or there is clinical proof of concept with cervical cancer. But beyond that, we actually presented pre- or iconic presented preclinical data late last year in pancreatic, I think head and neck, gastric cancer, and there were several other solid tumors that we haven't explored preclinically yet. So the opportunity is broad.

Gary with Bank of America.

Yeah.

Hey, guys. Thanks for taking my question.

The one just a housekeeping so when you do update cosmic 312, I'm wondering if we're actually going to get.

Hazard ratios like we did with the 90 or update I believe with Michael or there was an issue of a materiality and the need to disclose that because it was so important to the business, whereas I wonder with HCC. If that's the same situation and then second.

Peter Lawson: Great, thanks for that, guys. Hey, thanks for taking my question. One, just a housekeeping question.

Second question just on the.

The second paragraph for challenge to Cabo from Teva It looks like they are certifying on some of the later expiring patents around the formulation of method of use of these arent patents that are being disputed in the M. S. N case. So just wondering if the reason why is because you chose not to enforce those patents or.

Michael M. Morrissey: So when you do update Cosmic 312, I'm wondering if we're actually going to get hazard ratios like we did with the 9ER update. I believe with 9ER, there was an issue of materiality and a need to disclose that because it was so important to the business, whereas I wonder with HCC if that's the same situation. And then, second question, just on paragraph 4 of the challenge to Cabo from Teva, it looks like they're certifying on some of the later expiring patents around formulation and method of use.

And the reason I ask is if you look more of it is getting added to the M. S. N case, and so just wondering because it seems like the street's assuming that this product is going to go off of the quest in 2026.

Yeah. Thanks for the question of it's Mike I'll try to address both of them. So on the first question about the cosmic 300, <unk> two dee.

Michael M. Morrissey: These aren't patents that are being disputed in the MSN case, so just wondering if the reason is because you chose not to enforce those patents or, and the reason I ask is that it seems like more IT is getting added to the MSN case. And so just wondering, because it seems like the streets are assuming that this product is going to go off the quiz in 2026. Thanks. Yeah, thanks for the questions. It's Mike. I'll try to address both of them. So on the first question about the Cosmic 312 data,

Data.

The press release when that finally hit the top line results again, we are our processes to normally put in some level of data.

I wouldn't want to speculate on what that would be today, but at some level of data to provide a framework for the relative activity.

Because it's so material to us I would argue that 312 is probably as important as the <unk>.

<unk> is relative to the size of that market them the of.

The opportunity there in terms of the relatively nascent opportunity compared to where renal is currently so so.

Michael M. Morrissey: press release, when that finally hits top line results again, we

Michael M. Morrissey: Our practice is to normally put in some level of data, and I wouldn't want to speculate on what that would be today, but some level of data to provide a framework for the relative activity because it's so material to us. I would argue that 312 is probably as important as 90R is relative to the size of that market and the opportunity there in terms of a relatively nascent opportunity compared to where renal is currently.

Really I think continue that practice with the details will be defined when we get the data in the.

We understand what we've got okay in terms of the.

The second end of from Teva I think you I think you've covered all the facts pretty well so.

Again, as we mentioned in our filings and our press release.

The second <unk> came in.

Recently, the paragraph four letter again, the only challenging.

Three Orange book listed patents that expire in 2031 or later. So this is this is relatively new news to us. So I certainly wouldn't want to speculate on what theyre thinking on what theyre doing or how were of.

Michael M. Morrissey: So, you know, we'll certainly, I think, continue that practice, where the details will be defined when we get that data and we understand what we've got. The second, anda from Teva, I think you covered all the facts pretty well. So, you know, again, as we mentioned in our filings, in our press release, that second anda came in recently, paragraph four letter. Again, they're only challenging three Orange Book listed patents that expire in 2031 or later, so this is relatively new.

Thinking about it ourselves or how we might proceed of.

It's something that we're certainly not surprised by any shipment of reform as we've said before.

We expect these types of challenges to come in when you've got.

Great compounds with great data and certainly growing revenues and the <unk>.

We have strong data of strong IP.

Michael M. Morrissey: It's news to us, so I certainly wouldn't want to speculate on what they're thinking.

Great team, who are pursuing this very very aggressively.

Michael M. Morrissey: want to speculate on what they're thinking about what they're doing or how we're thinking about it ourselves or how we might proceed. You know, it's something that we're certainly not surprised by in any shape or manner reform. As we said before, you know, we expect these types of challenges to come in when you've got great compounds with great data and certainly growing revenues. And, you know, we have strong data and strong IP.

Has every intention to continue to defend our patents vigorously.

To all of the legal challenge of channels that we've got and we will provide updates as necessary.

Alright, thank you.

Hey, Jason.

Your next question comes from the line of our cash to worry with Wolfe research.

Michael M. Morrissey: It's a really great team who are pursuing this very, very aggressively, and we have every intention to continue to defend our patent estate vigorously through all the legal channels that we've got, and we will provide updates as necessary. All right. Thank you. Hi, this is Amy Leon from Akosh.

Hi, This is Amy Li on for cash thinks I'm expecting a question. So the first question on RCC are it seems like your current guidance baking in around 13 months of durability on the treatment do.

Do you see any sort of upside to this number could PFS get better with longer follow up and how we'll cosmic 313 impact the.

And then I have another one in HCC.

Yeah, Hi, Amy this is P. J thanks for the question.

I won't comment specifically on how we are thinking.

Patrick J. Haley: Thanks so much for taking our questions. So the first question on RCC, it seems like your current guide is baking in around 13 months of durability on treatment. Do you see any sort of upside to this number? Could TFS get better with longer follow-up? And how will Cosmic 313 impact this? And then I have another one on ATC.

Thinking about modeling duration, but I think if you look at the the PFS in the study.

It certainly.

Very strong in patients.

In these clinical studies of the combinations in the certainly the Navy. Our study are on therapy for the year and a half for potentially longer and I think it's important to remember that.

Michael M. Morrissey: Yeah, hi Amy, this is PJ. Thanks for the question. I won't comment specifically on how we are thinking about modeling duration, but I think if you look at the PFS in the study, it's certainly very strong in patients in these clinical studies of the combinations, and certainly the 90R study are on therapy for, you know, a year and a half, potentially longer. and I think it's important to remember that, you know, the data as these studies mature and get presented, sometimes it's not the median durations, the mean or average durations continue over time, but I'll kind of leave it at that.

The data as the studies maturing of presented.

Sometimes the.

It's not the median duration of the mean or average durations.

<unk> to increase over time, but all cash.

I'll leave it at that but we're certainly.

Very optimistic about the opportunity for revenue growth as I mentioned in my.

The prepared remarks, and I think.

The early days force of the launch so certainly look forward to.

Getting more and more patients on the regimen and then.

Refills the.

Reflecting the patients benefiting from that for us for some time to come.

Great. Thanks, so much of the color and then on H D. C. Given the we're not seeing much of the differentiation on safety and efficacy with the early cabling Evo common combo data from Checkmate, Oh, four O what the internal expectation on how cosmic 312 of stack up against and brave or leap of low too.

And what would you consider as competitive data internally.

Yeah, Hey, it's Mike. Thanks for the question I think it's really challenging to do any kind of cross trial comparisons between a global pivotal trial.

Michael M. Morrissey: But we're certainly, you know, very optimistic about the opportunity for revenue growth, as I mentioned in my prepared remarks. And I think, you know, it's the early days for us in the launch. So certainly look forward to getting more and more patients on the regimen and then refills; they're reflecting patients benefiting from that for some time. Great, thanks so much for the color. And then on HCC, given that we're not seeing much of a differentiation on safety and efficacy with the early Cabo and Evo combo data from Chexmate 040, what's the internal expectation on how Cosmic 312 will stack up against Embra Yeah, hey, it's Mike. Thanks for the question.

One was two different molecules compared to what.

What we had with the overall, which had a doublet or triplet debt were different from embraced.

Not only that but the.

It was smaller of isn't it was really non randomized to the control.

The mix of first and second line patients. So I wouldn't I wouldn't draw. The same conclusions you are around the around how the how similar of that data might be for all kinds of reasons. So.

Michael M. Morrissey: I think it's really challenging to do any kind of cross-trial comparisons between a global pivotal trial, one with two different molecules compared to what we had with 040, which had, you know, a doublet and a triplet that were different from Embrave. Not only that, but it was smaller, it was really non-randomized to a control, and it had a mix of first-and-line patients. So I wouldn't draw the same conclusions you are around how similar that data might be for all kinds of reasons. So, look, we're very excited about the opportunity. You know, certainly when you look at how we designed and enrolled.

Look we're very excited about the opportunities certainly when you look at how we how we designed and enrolled 312 relative to embrace popular.

Populations are very similar obviously of Tesla.

Is the same in both their relatively contemporaneous trials of lot of similar sites and investigators. The only difference is is cabo versus versus Bevacizumab and you can look at the single agent activity for those two agents across various tumor types.

They come to your own conclusions about how Cabo Mike for out there relative to the best so.

End of the day, you've got a run of the Trialing.

Michael M. Morrissey: 312 Relative to embryo populations, they're very similar. Obviously, at Tezzo it is the same in both. They're relatively

Get the data and look at the P values of Mint and the hazard ratios in the well.

Go off of that to.

Michael M. Morrissey: is the same in both. They're relatively contemporaneous trials with a lot of similar sites and investigators. The only difference is Cabo versus Bevacizumab. And, you know, you can look at the single agent activity for those two agents across various tumor types and, I think, come to your own conclusions about how Cabo might fare out there relative to Bev. So, at the end of the day, you've got to run the trial and, you know, get the data and look at the P values and the hazard ratios. And, you know, we'll go off that to really judge our conclusions as we go forward. Thank you so much. Hey guys, this is Walidon for Peter.

It really judge our conclusions as we go forward.

Thank you so much thank you.

Your next question comes from the line of Peter Lawson with Barclays.

Yeah.

Hey, guys. This is wahid on for Peter.

Thanks for taking my questions.

Of course to Hong Kong.

Cosmic <unk> one.

So you're still waiting to do the analysis per foot.

When can we potentially see the data and what are you looking for.

And that data set to sort of not only support approval, but hope to provide.

Full of offering in prostate cancer.

No.

Occasionally you wanted to take that one.

Sure. Thank you. Thanks for the question, Yeah, I think regarding cosmic <unk> one.

Gisa Schwab: Thanks for taking our questions. I had a question on Cosmic O2-1. I know you're still waiting to do the analysis there, but when can we potentially see the data? What are you looking for in that data set to sort of not only support approval but help you provide a competitive offering in prostate cancer? And then I have a follow-up. Keseel, do you want to go ahead and pick that one?

Certainly very pleased with the progress made in the study of two large phase <unk> trial of its been enrolling really well.

We're very excited about the data and and.

And as we look at the day can be seeing of various cohorts mature very nicely and we would expect to begin presenting results across the various cohorts.

This year and next.

And so with regards to moving forward, then and CRP T.

Gisa Schwab: Sure, thanks for the question. Yeah, I think regarding Cosmic O2-1, we are certainly very pleased with the progress made in this study. It's a large Phase 1B trial, and it's been going really well.

Likewise here as I mentioned earlier in the call.

To obtain the B R of ski the independent Radiology review for cohort six.

Gisa Schwab: We are excited about the data, and as we look at the data, we're seeing various cohorts mature very nicely, and we would expect to begin presenting results across various cohorts later this year and next. And so with regard to moving forward then in CRPC, likewise here, as I mentioned earlier in the call, we're looking to obtain the BRC, the Independent Radiology Review for cohort 6 in the next few weeks, a couple of months, in the mid-year time frame.

And the next few weeks of couple of months.

In the midyear time frame.

And as the.

With outdoor and of course earlier on as well, there's a lot going on in the next couple of months.

With the planned NDA filing for cosmic 311.

And also it would be H E C T.

Top line readout in the second quarter as well.

The CRP T top line data for cohort six being in the experience well, so certainly a lot of important milestones coming up.

Gisa Schwab: And as without dying, of course, earlier on as well, there's a lot going on in the next couple of months with the planned SNDA finding for Cognic 311 and also the HVC top line readout in the second quarter as well, and the CRPC topline data for cohort 6 being in the mixed there as well. So certainly, a lot of important milestones coming up. But we would expect to, of course, announce important data as we have it and obtain it.

But we would expect to of course to announce important data as we have them.

And obtain them and that goes for this cohort as well and then look forward to presenting the data and.

Scientific conferences in peer reviewed journals as well.

So thank you that's really helpful.

On your excellent linked to when can we see data from the phase <unk> studies.

Yeah, So ex the one and two is making good progress as I mentioned earlier the smell day.

Gisa Schwab: And that goes for this cohort as well. And then I look forward to presenting data at scientific conferences and peer-reviewed journals. Thank you. That's really helpful.

Phase one study in page one be evaluation is moving along.

In general I think.

As I mentioned also a little bit earlier.

The building here on a lot of experience and the successful development of Cabozantinib and with that Bill.

Gisa Schwab: Just on your Excel 92, when can we see data from the Phase 1B studies? Yeah, so Xcel 092 is making good progress, as I mentioned earlier as well. The phase 1 study in the Phase 1B evaluation is moving along. In general, I think, as I mentioned a little bit earlier, we're building here on a lot of experience and the successful development of Kavigantinib, and with that, we feel that the program is importantly at de-risk with that experience.

Feel that the program is importantly, it derisked with that experience, we are making progress in the dose escalation for single agent, except one or two and the combination with checkpoint inhibitors accused of need them up.

Notably.

And as we are expecting or have expected from a combo of experience. We're beginning to see preliminary promising antitumor activity in heavily pretreated phase one patients.

And we also have already presented the pharmacokinetic data.

And we're seeing the safety profile of that is consistent with our expectation of knowledge of the pathway.

Gisa Schwab: We are making progress in the dose escalation for the single agent, Excel O92, and the combination with checkpoint inhibitors at CISDLLLISO2, notably. And, as we are expecting or have expected from our Cabo experience, we're beginning to see preliminary promising antitumor activity in heavily-pretreated phase one patients. And we've also presented the pharmacokinetic data, and we're seeing a safety profile that is consistent with our expectation and knowledge of the pathway.

So with that I think we are.

We're very very focused on driving the program forward and introducing for the combinations.

As I mentioned on the call a little bit earlier.

And we certainly also expect to drive forward with the development program towards the charge of pivotal studies of intra and teacher in tier one data providing so.

Certainly with that.

Phil will.

<unk> day job on.

Gisa Schwab: So with that, I think we are very, very focused on driving the program forward and introducing further combinations. As I mentioned on the call a little bit earlier, and we certainly also expect to drive forward the development program towards the start of pivotal studies in 2021, data provided. And so certainly with that, we also will present data on the Excel-O-192-Ler-N combination when the time comes, but we'll laser focus on advancing the development program as the primary priority. Great, thank you so much for taking the time to answer the question. Thank you.

The excellent one of two alone or in combination when the time comes but we're laser focused on advancing the development program.

As the primary priority.

Great. Thank you so much for taking the questions. Thank.

Thank you.

Yeah.

Your next question comes from the line of Andy I see with William Blair.

Oh, great. Thanks for taking my questions and congratulations on the flow out quarter.

But two four P J.

Thanks for all of those commentaries on the initial trajectory of the top of watch so I am interested in knowing taking the macro view of you mentioned that the Teekay a PKI market grew 19%.

I remember you mentioned about kind of the shrinking market during the day.

The first of the COVID-19 pandemic can you provide us with some commentary about what you're seeing relative to kind of the diagnosis rate patient pool, and where we are in the synthetic.

Patrick J. Haley: Great, thanks for taking my questions, and congratulations on a blowout quarter. But two for PJ, thanks for all the commentary on the initial trajectory of the Cople launch. So I am interested in knowing, you know, taking a macro view, you mentioned that the TCA market grew 19%. I remember you mentioned about the kind of shrinking market during the death of the COVID-19 pandemic. You provide us with some commentary about what you're seeing relative to the diagnosis rate, patient pool, and where we are in the pandemic. Yeah, Andy, this is PJ.

Yes, Andy this is P. J. Thanks for the question certainly happy to provide a little more commentary there.

Mentioned.

We did see in Q1.

According to the.

The acuity of data and our ex us for the for the market basket as we define it <unk>.

<unk> grew by 19%.

Pablo medics.

For <unk> ex grew 31% quarter over quarter, so very pleased with that and as I mentioned.

Patrick J. Haley: Thanks for the question. I'm happy to provide a little more commentary there. As you mentioned, we did see in Q1, according to the QVA data, that NRX is for the market basket, as we define it. CISV grew by 19%.

We were the only product in that market basket to grow share so ex.

Excited with regards to that.

And as we mentioned it was driven by the.

The combination of the launch so that's great I do think with.

Regards to kind of what we're seeing here.

Hearing.

Anecdotally from our customers.

As things are.

Patrick J. Haley: CaboMedics for NRX grew 31% quarter over quarter, so very pleased with that. And as I mentioned, we were the only product in that market basket to grow share. So excited with regards to that, and as we mentioned, it was driven by the, the combination launch, so that's great. I do think, you know, with regards to kind of what we're seeing and hearing anecdotally from our customers is, you know, things are obviously with regards to the pandemic, it is regional, it's varied, and things are dynamic and they do change, but, you know, generally we see things getting back, to some semblance of normalcy and you know I would expect that as we get deeper into the year that will kind of continue and certainly helping us with access to our customers and education of them and, you know, we're hearing from them that things are, I mentioned kind of slowly getting back more to normal, but I think there's still some, you know, some opportunity for that to continue to improve. Okay, that's helpful, thank you.

With regards of the pandemic. It is regional is varied and things are dynamic and the new change.

Generally we see.

The things getting back.

To some semblance of normalcy and I would expect debt as we get.

Deeper into the year of that will kind of continue its certainly helping us with access to.

To our customers in the education of them and we're hearing from them. The things are I mentioned kind of slowly getting back.

More to normal, but I think theres still some.

Some opportunity for that to continue.

Improved broadly.

Okay.

Thank you.

And also for you know.

Regarding the FDA at home glass.

Weak earnings.

Potential implications for the second line HCC market dynamics.

I think of the panelists recommended pulling off the though the retaining keytruda the playful in that study.

Yeah. Thanks.

Thanks for the question again, Andy as P. J.

Certainly something we're tracking very closely with regards to all of those.

Patrick J. Haley: And also, regarding the FDA adcom last week, any potential implications for the second line HEC market dynamics? I think the panelists recommended pulling off Diva but retaining key treaters label in that. Yeah, thanks for the question again, Andy, is PJ.

Obviously, we won't speculate on what FDA will do there, but what I would say with regards to.

Opdivo or even generally monotherapy in HCC.

Primarily in the second line setting.

As we've talked about for some time now with the terms of Bev.

Being approved for about a year now.

The kind of first line combination market.

Becoming standard of care of there what we've seen as the shift of of Io utilization from second line monotherapy going to the first line of while that Hasnt completed.

Patrick J. Haley: You know, certainly something we're tracking very closely with regard to all of those. I obviously won't speculate on what FDA will do there, but what I would say with regard to, you know, Optiva or even generally monotherapy in HCC, which is, you know, primarily in that second line setting. As we've talked about for some time now with Tezo Bev being approved for about a year now and building kind of that first line combination market becoming standard of care there, what we've seen is that shift of IO utilization from second line monotherapy going to the first line. While that has completed, that shift is kind of already well underway and happening, which opens up more room for single agent TKI utilization in the second line.

That shift has kind of already.

All underway is happening.

Which opens up more room for.

Simulated <unk> utilization in the second line. So I think if anything depending on how of how that plays out or the kind of of the coverage there of just.

It might potentially accelerate that a little bit, but I think the market shifting.

And obviously, we will see how 312.

Reads out soon and there'll be more potential for that market to dynamically change and I think importantly, there in HCC, we are seeing and expect to continue to see more patients coming into the so to speak first line funnel with more and more.

Patrick J. Haley: So I think, you know, if anything, depending on how that plays out, or the kind of coverage there just, you know, might potentially accelerate that a little bit. But I think the market's shifting as it is, and obviously we'll see how 3-1-2 reads out soon, and there'll be more potential for that market to dynamically change. And, you know, I think important there, in HCC, we're seeing and expect to continue to see more patients coming into that, so to speak, first line funnel with more and more, you know, therapeutic options that are going to be helpful for patients. Thanks, PJ. And maybe one kind of strict, cheap question for Mike or Peter.

[noise] therapeutic options that are going to be helpful for patients available.

Thanks, P J and maybe one kind of strategy question for us for the Michael Peter.

I'm just wondering can connect flexes leverages, the mystery foundation and kind of the new really gained capabilities in biologics.

Outside the box so basically beyond the traditional framework of kind of like of antibody linker payload cadre of for ADC.

Thanks, Andy that that's of Great question for Peter.

Much of it over to him.

Thanks, I think it's of Great question period.

I think Youll view of it is essentially correct of if you look at the history of of Adcs, and we kind of about 20 years of ADC discovery and development at this point.

Patrick J. Haley: I was just wondering, can Xlexis leverage its chemistry foundation and kind of the newly gained capabilities and biologics to think outside the box? So basically, beyond the traditional framework of kind of like an antibody link payload contract for ADC? Thanks, Andy. That's a great question for Peter, so I'm going to pass it over to him. Yeah, thanks, honey. It's a great question, period.

Of the vast majority of the payloads of people who have used to full of into really three.

Three of four classes of mechanism of action that has predominantly been microtubule.

The stabilizing agents with one kind of another or DNA damaging agents took away some range of coated price inhibitors. So.

Peter Lawson: And, you know, I think your view of it is essentially correct. If you look at the history of ADCs, and we've had, what, 20 years of ADC discovery and development at this point, the vast majority of the payloads that people have used have fallen into, you know, broadly, three or four classes of mechanisms of action, and they've predominantly been microtubial destabilizing agents of one kind or another, or DNA damaging type agents, topoys, some inhibitors.

I think there is.

One of the interest in trying to develop novel payloads, starting to see it a little bit obviously of the number of folks working on immune stimulatory payloads of various classes of.

As you pointed out with the.

Kind of 20 plus year history.

Medicinal chemistry here.

And escaped our notice of this might be an attractive area to explore further.

There's a lot of opportunity there and I think it would dovetail very well with the collaborations that we established late last year, we've MB and Cadillac to access the site specific conjugation technologies.

Peter Lawson: So I think there's, you know, a lot of interest in trying to develop novel payloads. We're starting to see them a little bit. Obviously, there are a number of folks working on immune stimulatory payloads of various classes. So if you point out, with our kind of 20-plus year history in medicinal chemistry here, it hadn't escaped our notice that this might be an attractive area to explore further. I think there's a lot of opportunity for them there.

And the ongoing efforts that we have to assemble the kind of essentially of library of.

Antibodies bind us that would be attract against attractive targets for ADC either through our inventor of collaboration.

All of them Opportunistically through the collaboration so.

The licensees as we did with the Wuxi late last year and this week, we've got the map. So great question States say stay tuned on that point and.

Peter Lawson: I think it would dovetail very well with the collaborations that we established late last year with MBE and Catalan to access their site-specific conjugation technologies, and the ongoing efforts that we have to assemble kind of essentially a library of antibodies and binders that would be attracted against attractive targets for ADCs, either through our in Venera collaboration, or opportunistically through the collaborations of all the licenses we did with Wushi late last year and this week with Gammaab.

Look forward to updating everyone broadly on what we're doing in ADC is going forward.

Thank you so much Peter.

Youre welcome Andy Thank you.

Your next question comes from the line of Huron wherever with Cowen.

Hey, this is Dave on for your own thanks for taking my question.

Just a follow up to one of the previous questions about Cabo you guys are.

Peter Lawson: So great questions, stay tuned on that point, and look forward to updating everyone broadly on what we're doing in ADC going forward. Thank you so much, Peter. You're welcome, Annie. Thank you. Hey, this is Gabe on for yourself. Thanks for taking my question. Just a follow-up to one of the previous questions about Cabo. You guys are, you know, obviously making great progress, quarter over quarter in first line, renal.

Obviously, the great progress quarter over quarter in first line renal cell could you share of what fraction of all in our ex us are going to cover the Q1 compared to Q4.

A little color, maybe on what feedback you're getting from physicians or payers as to why they may be sticking with other one O option first line options. Besides Cabo opdivo in certain cases as opposed to.

Embracing many are pretty much across the board. Thank you.

Patrick J. Haley: Could you share what fraction of all NRXs are going to Cabo in Q1 compared to Q4? And maybe some color on what feedback you're getting from physicians or payers as to why they may be sticking with other 1L options, first-line options besides Cabo-Abdevo in certain cases, as opposed to, you know, embracing 90R pretty much across the board? Thank you. Gabe, this is PJs.

Yeah. Thanks for the question Gabe This is P. J so.

I guess, the first I'll start with the numbers in the data.

What we had in Q4 was an Rx market share of the market basket of 32% and in Q1 the.

<unk> market share for <unk> was 36% and the volume growth for Cabo medics Q.

Q1 over Q4 was 31% and I guess the way the way I kind of think about that is we're really pleased with the that's.

Patrick J. Haley: So I guess I'll start with the numbers and the data. You know, what we had in Q4 was an NRX market share of the market basket of 32%. And in Q1, the NRX market share for KhaboMedics was 36%, and the volume growth for Kaobamatic's Q1 over Q4 was 31%. And I guess the way I kind of think about that is we're really pleased with the start there, particularly since our approval came in late January, and we're seeing, actually, you mentioned payers, we're seeing, really, you know, minimal pushback on the payer side of the data, so sort of.

Of that start there, particularly since our approval came in late January and we're seeing actually you mentioned payers we're seeing.

Really.

Minimal.

Pushback on the payer side of the data so sort of clear cut that's great sourcing great.

Adoption of policies broadly from a payer perspective, and I think the.

The physician perceptions as I mentioned of the data really good.

And.

We're really pleased with that level of education I think we have continued opportunity to continue to educate.

Really in the community, particularly the things open up more with regards to.

After the somewhere around the pandemic and I think.

The more we get to get in front of physicians with our database from what we're seeing will continue to make progress there certainly optimistic.

Patrick J. Haley: adoption and policies broadly from a payer perspective. And I think, you know, the physician perceptions, as I mentioned, of the data are really good. And, you know, we're really pleased with that level of education. I think we have a continued opportunity to continue to educate the community, particularly as things open up more with regard to, you know, optimism around the pandemic. And I think the more we get to get in front of physicians with our data, based on what we're seeing, will continue to make progress. They're certainly optimistic. Great, thank you. Hey guys, thanks for taking my questions. Congratulations on the Great

Great. Thank you.

Our next question comes from the line of Michael Schmidt with Guggenheim.

Hey, guys. Thanks for taking my questions. Congrats on the great first quarter I actually had a couple of pipeline questions as well first perhaps an excellent <unk> mechanistic question here. So it's pretty obvious that the shorter half life of this molecule relative to cavil medics.

We will probably make it easier to dose and Nash the toxicity profile could.

Could you just help us understand how that mechanistically could translate into a potential improved efficacy benefit relative to the experience with Cabo medics.

Patrick J. Haley: first quarter. I actually had a couple of pipeline questions as well. First, perhaps, on XL092, a mechanistic question here.

And then I had the second question.

Yeah, why don't we thanks, Michael its Mike why don't we let Peter take a crack at that and maybe Gisela can provide some color commentary to go ahead Peter.

Peter Lawson: It's pretty obvious that the shorter half-life of this molecule relative to cabomatics will probably make it easier to dose and manage the toxicity profile. Could you just help us understand how that mechanistically could transfer into a potential improved efficacy benefit relative to your experience with cabomatics? And then I had a second question. Yeah, thanks Michael, Mike, why don't we let Peter take a crack at that, and maybe Gisla can provide some commentary too? Go ahead, Peter.

The goal of owning too as you correctly stated we want to maintain the overall target profile of Cabozantinib hitting all of the same age of targets and pretty much the same.

Ratios.

So that we could build off of the extensive experience that we have with cabozantinib.

Clinically.

Single agent and in combination, but to reduce the offline.

Sure.

Some of appropriate chemical modifications aimed at doing just that and heavily.

Played out well in the clinic.

Peter Lawson: Yeah, so I think the goal with 092, as you correctly stated, was one to maintain the overall target profile of Kavanaugh, hitting all the same major targets in pretty much the same ratios so that we could build off the extensive experience that we have with Kavizantinib clinically, both as a single agent and in combination, but to reduce the half-life. So you have made some appropriate chemical modifications aimed at doing just that, and, happily, that has played out well in the clinic.

The aim as you stated is to provide a.

The way to manage the dosing and site management of side effects.

As far as widely as possible and the shorter half life. Certainly helps you do that so I would say overall the anytime you can.

Optimize your dose and dosing for individual patients you maximize the chance of providing them with the with clinical benefit.

Great. Thank you Gisela.

The foster.

Yeah, and I agree with everything Peter said and perhaps just to add of course, it. It's about continued growth and as patients benefit to maintain dosing for the duration of soundness patient device benefit.

Peter Lawson: The aim, as you stated, is to provide a way to manage the doses and site management of side effects as fast as possible, and a shorter half-life certainly helps you do that. So I would say overall, any time you can optimize your dose and dosing for individual patients, you maximize the chance of providing them with clinical benefit. Great, thank you. Gisla, any thoughts there?

The other thing to offer perhaps in addition, and it's one of additional spot is of course combinability.

And there I think facile dose.

Adjustment, whereas the shorter half life of comes in handy.

Gisa Schwab: Yeah, I agree with everything Peter said, and perhaps just to add, of course, it's about continued dosing and as patients benefit, to maintain dosing for the duration as long as patients enjoy benefits. The other thing to offer, perhaps in addition is one additional spot is, of course, combineability. And there, I think, facile dose adjustment was a shorter half-it comes in handy. That is perhaps another consideration.

That is perhaps another consideration.

Great. Thanks, and then just one on ex.

The one or two.

We've noticed a lot more interest now in all of the sales cycle targets for example of such as the CDK to or we won and the others P 53 et cetera, just remind us where CDK seven states in here and whether that's a.

Target debt is expected to be broadly active or whether this is by the end of <unk>.

After the cat seven would be.

Gisa Schwab: Great, thanks. And then just one on Xcel 102. We've noticed a lot more interest now in novel cell cycle targets, for example, such as CDK2 or We1 and others, P53, et cetera. Just remind us where CDK7 sits in here and whether that's

Preferentially pursuing a certain genetic contact so of biomarker positive patient population. Thank so much.

Yes. This is the state of he'd be happy to take to take that one so again, you're absolutely right. There has been another uptick in interest in CDK is broadly and I would say CDK seven specifically.

Peter Lawson: a target that is expected to be brought

The CDK seven fifth essentially upstream of the classical sales cycle kind of Cdk's, which of CDK, one and two.

Peter Lawson: widely active, or whether this is, whether inhibition of CDK7 would be, you know, preferentially pursued in a certain

And is responsible for activating those kind of any of us. If theres also upstream of of CDK, four and six which of which were obviously the the targets with the cyclic close of approved of approved drugs. So it does play a major role in orchestrating orchestrating the cell cycle.

Peter Lawson: a certain genetic contacts or biomarker population. Thanks so much. Yeah, this is Peter.

Peter Lawson: I'd be happy to take that one. So again, you're absolutely right. There's been another uptick in interest in CDKs broadly, and I would say CDK 7 specifically. CDK7 sits actually upstream of the classical cell cycle kind of CDKs, which are CDK 1 and 2, and is responsible for activating those kinases. It's also upstream of CDK Forums Fix, which are obviously the targets for the cyclic class of approved drugs. So it does play a major role in orchestrating the cell cycle.

There is also maybe some role for it as well in regulating the initiation of of transcription towards the ability to either directly phosphorylate transcription factors.

The health immediately to the assembly of the kind of transcription of pre initiation complex of it plays more than one rule.

It seems proof of predominantly on the on the sell cycle side. So if you look at the profile of CDK <unk> inhibitors, including the room.

So in vitro and in vivo. The it's broadly active as you might expect to sort of think working on the sales cycle.

Peter Lawson: There may also be some role for it as well in regulating the initiation of transcription, so its ability to either directly phosphory transcription factors or help mediate the assembly of the kind of transcriptional pre-initiation complex. So it plays more than one role.

A lot of the indications that are being contemplated.

The do tend to focus more on tumors that have genetic lesions of the factory activity of CDK of such as the deletion for example, or.

The vacations and various likely disease.

Peter Lawson: But it seems predominantly on the cell cycle side. So if you look at the profile of C2K and 7 inhibitors, including our own, certainly in vitro and in vivo, it's broadly active, as you might expect for something working on the cell cycle. A lot of the indications that are being contemplated do tend to focus more on tumors that have genetic lesions that affect the activity of CDKs, such as RB deletion, for example, or amplifications in various cycling genes.

One of the obvious place for it.

Essentially as the.

Of the treatment in the tumors have become resistant to the CDK four and six inhibitors from CDK seven as of stream of those so.

So there's a lot of places to go the reputedly potentially with the CDK <unk> inhibitor and I think that's driving the helping drive a lot of the interest including our own.

Super Thanks, so much of our interesting early pipeline marching here.

Michael.

Your next question comes from the line of Jay Olson with Oppenheimer.

Peter Lawson: Another obvious place for it is potentially as a treatment for tumors that become resistant to CDK-46 inhibitors, and CDK-7 is upstream of those. So there's a lot of places to go, they're reputedly potentially with a CDK, so an inhibitor, and I think that's driving, helping drive a lot of the interest, including our own, Super, thanks so much, very interesting, early pipeline marching here Thank you, Michael.

Right.

Oh, Hey, congrats on all of the progress and thanks for taking the questions.

Contact zero one is successful could you comment on the potential to move Carlo plus the <unk> or maybe <unk> plus the <unk> into first line non small cell lung cancer and would that depend on PD, one expression levels or some other biomarker driven approach.

Yeah. Thanks, Dave do you want to take that one.

Sure. Thank you yeah. So just.

The two explained contact of one of course is in the previously treated patient population, who have received prior checkpoint inhibitor.

Peter Lawson: Oh, hey, congrats on all the progress and thanks for taking the questions. If Contact Zero One

Gisa Schwab: If 01 is successful, could you comment on the potential to move?

Gisa Schwab: Cabo plus a tezzo or maybe 092 plus a tezzo into first-line non-small cell lung cancer, and would that depend on PD1 expression levels or some other biomarker-driven approach?

And that of Phase III studies ongoing with already presented data from the cosmic <unk> two one net.

Steady and have seen encouraging activity for the combination of Cabo and tangible.

Gisa Schwab: Yeah, Jay. Do you feel you want to take that one? Sure, thank you. Yeah.

Gisa Schwab: So just to explain, contact of one, of course, is in the previously treated patient population who have received prior checkpoint inhibitors, and that phase three studies ongoing, we've already presented data from the Cosmic O21 study, and I've seen encouraging activity for the combination of carbon and atazel in this setting in ICI pre-treated patients. I think as we're thinking about earlier lines of therapy and perhaps also combinations that could then be relevant for XLO92 as we go forward. I'm certainly very interested in the ataseal combination that is ongoing in this space with XLO92.

And the fitting and ICI pretreated patient.

I think as we're thinking about earlier lines of therapy and perhaps also.

Combinations that could then be a friend of event.

The score Excel on line two.

We go forward.

And are very interested in the.

A change of combination that is ongoing in the space with excellent one I'm too and further combinations and in certainly.

The the work that Genentech Roche is conducting in non small cell lung cancer, combining occasionally the month, but the ticket antibodies.

Interest and plenty.

The other some intriguing data and an earlier line setting whether or not that will be then confined to patients.

Selected by PD, one PDL one expression I think that's the remains can be seen and perhaps the opportunity when combining with.

Gisa Schwab: and further combinations and certainly the work that Genentec Roche is conducting in non-smouth lung cancer, combining Tizelizema with the tidet antibodies of interest, and they deal with some intriguing data in an earlier line setting. Whether or not that will be then confined to patients selected by P1, PDR1, PDR1, expression is something that remains to be seen, and perhaps there is opportunity when combining with TKI to broaden the patient population. So certainly, there is a lot to evaluate, but it's a very interesting space and a lot of opportunity, I think, for XO92 and also, of course, for COBS in Genoa.

T K I to broaden the patient population, so suddenly a lot too.

But it's a very interesting space and a lot of opportunity I think for them.

So on line two and also of course for Cabozantinib.

Thank you that's very helpful and if I could maybe sneak in another question on <unk> have you seen any preclinical data that shows potential synergy between <unk> and any of your early stage adcs or small molecules.

Yes, it's a great question.

That kind of work is actually in progress right now so I can't comment on it yet but.

Stay tuned.

Okay, great. Thanks for taking the questions.

Yes.

Gisa Schwab: Thank you, that's very helpful. And if I could maybe sneak in another question on 092,

Your next question comes from the line of Kennan Mackay with RBC capital markets.

Gisa Schwab: question on 092. Have you seen any preclinical data that shows potential synergy between 092 and any of your early stage ADCs or small molecules? Yeah, that's a great question. That kind of work is actually in progress right now, so I can't comment on it yet, but stay tuned. Okay, great. Thanks for taking the time to answer your questions. Hey, thanks for squeeze me in, and congrats on the quarter. A sort of qualitative question on the frontline market here.

Hey, Thanks for squeezing me in and congrats on the quarter sort of.

The qualitative question on the frontline market share I'm just wondering.

Where you are gaining more traction whether it's the academic community clinics and then some of the feedback we've had from some physicians that.

What's the I appreciate it most about the combination has the potential to induce super Super fast and deep.

See ours or their debt.

The PR and as a result of that there may be using it in.

Patients with bulkier tumors wanted to hear if.

That was something that the.

The team was hearing as well or.

Gisa Schwab: I'm just wondering where you're gaining more traction, whether it's academic or community clinics, and then some of the feedback we've had is from some physicians that, you know, what they appreciate most about the combination is its potential to induce super, super fast and deep CRs or very, very deep PRs. And as a result of that, they're making. Maybe using it in patients with bulkier tumors.

Whether it's just such a broad market to over the site.

And congrats again.

Yeah.

This is P. J thanks for the question.

As I mentioned I think the uptake is really it.

Has been broad and the feedback that we've received is that it really is.

The data are resonating across sort of a variety of critical.

Patrick J. Haley: Wanted to hear if that was something that the team was hearing as well or, you know, whether it's just such a broad market. True, I would say. Thanks and congrats again. Yeah, this is PJ.

The subset so to speak or.

To the specific as defining it as the IMTT risk category so favor.

Favorable intermediate and poor I'd say at this early stage, we're seeing it broadly.

Patrick J. Haley: Thanks for the question. You know, as I mentioned, I think the uptake is really, it has been broad, and the feedback that we've received is that it really is, you know, the data responding across sort of a variety of clinical, you know, subsets, so to speak, or, you know, if you want to be as specific as defining it as the IMDC risk categories. So favorable, intermediate, and poor, I'd say, you know, at this early stage, we're seeing it broadly, and I wouldn't really say differentially based on the early data, but stay tuned.

And I wouldn't really say differentially based on the early data, but stay tuned.

Your comment specifically about.

Kind of of symptomatic patients.

Meeting of response, that's something that.

Generally I think has been.

Hallmark of Cabos in mono therapy in the later setting, but certainly as physicians begin to see the data at <unk> I think that certainly of places.

It is thought of to be used.

Yeah.

And those types of patients which are certainly.

Gratifying that said even on the other end of the spectrum you see.

You see us doing really well in the favorable risk category.

And we've just recently gotten mtc and category.

Patrick J. Haley: You know, your comments specifically about, say, kind of a symptomatic patient, you know, needing a response, that's something that, you know, generally I think has been a hallmark of Cabo, even in monotherapy in a later setting, but certainly as physicians began to see the data in 90R, I think that's certainly a place it's thought of to be used in those types of patients, which is certainly, you And, you know, that said, even on the other end of the spectrum, you see us doing really well in the favorable risk category.

One of our recommendations across all of those risk groups of if that will continue to.

Provide momentum for us of particularly the net favorable setting but.

We're gratified.

Seeing uptake across all patient types and.

The hearing from physicians that is benefiting their patients.

Yeah.

Yeah.

They kind of anything else.

Patrick J. Haley: And, you know, we've just recently gotten NCCM category one recommendations across all those risk groups. So I think that will continue to provide momentum for us, particularly in that favorable setting. But, you know, we're gratified. We're seeing uptake across all patient types and hearing from physicians that it's benefiting. Take Cannon, anything else?

Yeah.

Okay, I mean, I don't think of it.

Take the next question. Please okay. Your next question.

Comes from the line of Paul Choi with Goldman Sachs.

Hi, Thank you good afternoon, everyone and let me also add my congratulations on the quarter My first question.

As for Gisela, just with regards to the the contact one and two programs I know you indicated that both of those those studies are enrolling but could you maybe indicate whether some early initial data from early early enrolled patients might be possible.

Operator: Okay, operator. The next question, please. Okay, your next question comes from the lineup. Choi with Goldman.

By later this year and then I had a follow up on the commercial or financial side from Chris.

Thanks, Yes on contact one of two and three for that matter all of these phase III studies involving patients globally.

Gisa Schwab: Hi, thank you. Good afternoon, everyone, and let me also add my congratulations on the quarter. My first question is for Gisla, just with regard to the contact one and two programs. I know you indicated that both those studies are enrolling, but could you maybe indicate whether some early initial data from early enrolled patients might be possible by later this year? And then I had a follow-up on the financial side for Chris.

And we're pleased with the progress on the studies for sure.

Day cab.

It's not expected to be available. This year. These are facing the relative sizable large phase III studies of.

Of course the.

Endpoints are at a time to event endpoints.

Depending on the study PFS and Norway.

Gisa Schwab: Thanks, yes. On contact one and two and three, for that matter, all of these phase three studies are involving patients globally, and we're pleased with the progress on the studies for sure, but data is not expected to be available this year. These are fairly sizable, large phase three studies, and, of course, the endpoints are time to event endpoints, depending on the endpoints. For example, study PFS and OS or OS itself

Itself, so that will take a little bit longer and the expected not before 2020 true.

Okay. Thank you for clarifying that and then.

One for Chris I think last quarter, you highlighted a seven 5 million inventory benefit I was wondering if you could quantify it for this quarter as well and then.

Just given the strong start to start to the year you left the guidance unchanged. So I was just curious you know what was the sort of thinking.

Chris Shibutani: So that will take a little bit longer and is not expected before 2020. Okay, thank you for clarifying that. And then, as a one for Chris, I think in the last quarter you highlighted a 7.5 million inventory benefit. I was wondering if you could quantify it for this quarter as well. And then, you know, just given the strong start to the year, you left guidance on change. So I was just curious, you know, what the sort of thinking was, at least behind not raising the low end of the revenue guidance.

At least behind not raising the low end of the revenue guidance. Thank you very much.

Hey, Paul Thanks for the question so on the inventory side I mean.

We didn't quantify at this time, but it's about 300 units.

It's in the $6 million range at our.

At our wholesaler acquisition cost of about $4 five if you think about it the net the net benefit perspective so.

Our net detriment to this quarter perspective.

And then.

And then.

The guidance.

Yes.

Chris Shibutani: Thank you very much. Hey, Paul, thanks for the question. So on the inventory side, I mean, we didn't quantify it this time, but it's about 300 units and, you know, in the $6 million range at our host seller acquisition costs and, you know, about four and a half if you think about a net benefit perspective, or a net detriment to this quarter.

From a guidance perspective.

We're very pleased with where we started the year.

Continued as Peter said it was we had about two months into the into the quarter for two months in the quarter from a from a performance perspective.

And we continue we're going to continue the monitor at the very dynamic market.

A lot of there's a lot of competition in the market and we're going to continue the and it's very early in the in the launch. So we'll continue to look at it and revisit it in the.

Chris Shibutani: And then, And then, Got you, yeah, sorry. From a guidance perspective, you know, we were very pleased with where we started the year. We continued, as PJ said, we had about two months into the quarter or two months in the quarter from a performance perspective. And, you know, we're going to continue to monitor it. It's a very dynamic market. There's a lot of competition in the market, and we're going to continue to do it. And it's very early in the process, in the launch.

In the future quarters.

Yeah.

Thanks for taking our questions and of course zone.

As a reminder, if you would like to ask a question press star one on your telephone.

Okay.

And your last question comes from the line of Stephen Willey with Stifel.

Hey, good afternoon, guys. Thanks for squeezing me in and congratulations on the quarter.

Just a couple of quick prostate questions. So I guess at time of the cohort six disclosure of indoor presentation.

Chris Shibutani: So, you know, we'll We'll continue to look at it and revisit it in future quarters. Thanks for taking our questions. As a reminder, if you would like to ask, just star one on your time. Your last question comes from the line of Stephen Willie with Steeful.

Will we see some of the.

Additional cohort.

All of our data that's been embedded within this cause of that go to one trial design in terms of I think there is a single agent of tens of a single agent Cabo cohort just wondering if.

Michael M. Morrissey: Hey, good afternoon, guys. Thanks for squeezing me in, and congratulations on the quarter. Just a couple quick prostate questions.

If you plan to present that in conjunction with.

Michael M. Morrissey: So, I guess, at the time of the cohort 6 disclosure and door presentation, will we see some of the additional cohorts, cohort data that's been embedded within this CosmicO trial, Cabo, just wondering, plan to present that in conjunction with co- Yes, Mike, it's probably a little bit too early to opine upon or speculate on how we'll roll all that out. You know, we understand the importance of the data relative to both keeping investors up to date on what's happening and also relative to a filing.

Cohort six.

The disclosure and then instead of a quick follow up.

Yes, Mike, it's probably a little bit too early to opine upon or speculate on how we'll roll all that out.

We understand the importance of the data relative to growth keeping investors up to date on what's happening, but also in relative to our filing so.

So stay tuned.

Let's get the <unk> done and then we'll roll out data at the appropriate time.

Perfect.

I guess in any of the regulatory dialogue you've had with FDA.

Do you think that of label here is going to be limited to patients with measurable disease at baseline or do you think that there is an opportunity that you could get a bit of a broader language that would allow you to.

Michael M. Morrissey: So, stay tuned. Let's get the BIRC done, and then we'll roll out the data at the appropriate time. And I guess in any of the regulatory dialogues you've had with FDA, would you think that a label here is going to be limited to patients with measurable disease at baseline, or do you think that there's an opportunity that you could get a bit of a broader language that would allow treating some of these patients that have bone? Yeah, look, I wouldn't want to speculate on the outcome of those discussions that we have, and I wouldn't I think it's probably safe to say that labels usually align with the populations that were studied.

Treat some of these patients that have bone only disease as well.

Thank you.

Yes look I wouldn't want to speculate on.

Of those on the outcome of those discussions that we have and I wouldn't want to talk about the discussions either.

I think it's probably safe to say that.

Labels, usually aligned with populations that were studied so I would think about it from that point of view I think thats couple of the safest way to go but.

Again, when we get that far.

Thinking about it.

The releasing that information, we will be happy to share that with you at the appropriate time.

Alright, thanks and congrats.

Thank you Steve.

At this time there are no further questions and so I will turn the call over to today's host Susan Hubbard Ms. Thank you yeah. Thank you Daphne and thanks, everybody for joining US today, certainly happy to take your follow up calls with any additional questions. You may have after we conclude thanks again.

Michael M. Morrissey: So I would think about it from that point of view. I think that's probably the safest way to go, but, you know, we'll, again, when we get that far, we're thinking about, you know, releasing that information. We'll be happy to share that with you at the appropriate time. All right, thanks. Yeah, thanks.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating and you may now disconnect.

Michael M. Morrissey: Thank you, Steve. There are no further questions, so I will turn the call over to today's host, Susan Hubman. Thank you, Stephanie. Thank you, Stephanie, and thanks everybody for joining us today. Certainly, happy to take your follow-up calls with any additional questions you may have after we can. Thanks again. Ladies and gentlemen, this concludes today's program, thank you for participating, and you may now discuss

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